Genetic variants associated with alcohol intake or metabolism have been proposed as unbiased and unconfounded markers of the effect of ingested ethanol or its metabolites (acetate, acetaldehyde)—an approach known as Mendelian randomization (12,13). A single nucleotide polymorphism (SNP) exists in the acetaldehyde dehydrogenase gene ALDH2, which encodes an enzyme unable to clear acetaldehyde and often causes individuals carrying the variant to abstain from alcohol or drink in moderation (14). The use of ALDH2 as an instrument has proved valuable in Mendelian randomization studies (15,16). However, the potential relevance of this variant is limited to East-Asian populations as it is absent in populations of European origin (17).
